The clinical management of patients with age-related maculopathy (ARM) has been revolutionized by non-invasive imaging of the retina at near-histological detail. Imaging is essential for educating patients about eye health and following disease progression, monitoring treatment outcomes, and specifying, designing, and validating new instruments. We propose translational research directed toward informing the clinical use of spectral domain optical coherence tomography (SD-OCT), which provides cross-sectional views of all chorioretinal layers, and fundus reflectance and autofluorescence (AF) imaging, which both provide en face (face on) views of the retinal pigment epithelium (RPE). We will exploit a unique resource of human donor eyes at different stages of ARM to produce gold standards for retinal image interpretation. Points of identification essential for maculopathy management and research using SD-OCT have not been systematically validated. We will obtain SD-OCT images of excised macula and optic nerve followed by high-resolution, wide-field histological cross-sections. Project MACULA (Maculopathy Unveiled by Laminar Analysis) will use aged normal, early ARM, geographic atrophy, and neovascular ARM to: 1. Identify features in SD-OCT images and corresponding histological cross-sections of the same eyes, with special attention to disambiguating combined signals from adjacent layers and identifying ARM- pathology beyond drusen. 2. Measure the thickness of each retinal layer, Bruch's membrane (BrM), and choroid across the macula and in comparison regions of peripheral retina. 3. Establish an electronic atlas of ARM pathology to inform next-generation tomographic imaging by scanning each tissue slide in its entirety and placing it an online digital pathology archive. The RPE, central to ARM pathogenesis, has been visualized clinically in the en face direction using both reflectance and autofluorescence (AF) signals, the latter from RPE lipofuscin. Project RPE Census will use chorioretinal whole mounts, DIC and confocal microscopy, and eyes of different ages and ARM status to: 4. Quantify RPE packing geometry at well-specified locations to generate a continuous mathematical function describing RPE topography; describe disruptions over drusen and basal deposits. 5. Quantify RPE AF at well-specified locations; identify AF correlates of RPE disruptions associated with drusen and basal deposits, using 3-dimensional reconstruction of confocal microscopy images Improved knowledge about macular anatomy will help inform assessment of risk for advanced ARM and the assessment of treatments. We anticipate that data will be used by opinion leaders in clinical imaging, instrumentation engineers, ophthalmic educators and illustrators, and developers of new animal models of ARM. The fundamental data that we obtain will be useful for this and future generations of imaging. PUBLIC HEALTH RELEVANCE: Because the retina is so readily visible through the eye's optics, clinical imaging is now an essential component of staging and monitoring patients involved in clinical trials for treatments of age- related maculopathy (ARM), the large and debilitating cause of vision loss among the elderly. We propose to improve clinical interpretation of two increasingly common retinal imaging methods (optic coherence tomography and fundus autofluorescence) by quantitative analysis of retina and choroid from human tissue specimens at different stages of ARM.